uPA accelerates elongation and directs pathfinding of retinal ganglion cells axons.

Axon growth and guidance are main cellular mechanisms for establishing functional neural circuits. The retinotectal system is the main model for studying the development of neural connections. The urokinase-type plasminogen activator (uPA) -in association with its receptor (uPAR)-triggers extracellular matrix proteolysis during cell motility. We have previously demonstrated that uPA promotes neuritogenesis by a combined proteolytic and non-proteolytic mechanism in the chick optic tectum. However, it is not known whether uPA participates in the axon growth and guidance of retinal ganglion cells (RGC) during the formation of retinotectal connections. The objectives of this work were to investigate whether uPA participates in axon growth and guidance of RGC. For this purpose, we performed immunohistochemistry against uPAR in retinotectal sections and studied the effects of uPA on: a) RGC axon growth in retinal explants and b) axon guidance in dissociated RGCs cultured and exposed to gradients of uPA produced in the Dunn’s chemotaxis chamber using time-lapse imaging. Results showed that uPAR is expressed in RGC axons, uPA exhibits a chemoattractant effect on RGC axons and increases the axon growth velocity by enhancing both maximum velocity and growth-phase velocity. Furthermore, we investigated the uPA-mediated signaling using immunocytochemistry and Western blot, demonstrating that uPA increases FAK activity in RGC axons. UBACYT 20020220100197BA